| First Author | Pelegrin P | Year | 2009 |
| Journal | EMBO J | Volume | 28 |
| Issue | 14 | Pages | 2114-27 |
| PubMed ID | 19536133 | Mgi Jnum | J:150838 |
| Mgi Id | MGI:3851882 | Doi | 10.1038/emboj.2009.163 |
| Citation | Pelegrin P, et al. (2009) Dynamics of macrophage polarization reveal new mechanism to inhibit IL-1beta release through pyrophosphates. EMBO J 28(14):2114-27 |
| abstractText | In acute inflammation, extracellular ATP activates P2X(7) ion channel receptors (P2X(7)R) on M1 polarized macrophages to release pro-inflammatory IL-1beta through activation of the caspase-1/nucleotide-binding domain and leucine-rich repeat receptor containing pyrin domain 3 (NLRP3) inflammasome. In contrast, M2 polarized macrophages are critical to the resolution of inflammation but neither actions of P2X(7)R on these macrophages nor mechanisms by which macrophages switch from pro-inflammatory to anti-inflammatory phenotypes are known. Here, we investigated extracellular ATP signalling over a dynamic macrophage polarity gradient from M1 through M2 phenotypes. In macrophages polarized towards, but not at, M2 phenotype, in which intracellular IL-1beta remains high and the inflammasome is intact, P2X(7)R activation selectively uncouples to the NLRP3-inflammasome activation but not to upstream ion channel activation. In these intermediate M1/M2 polarized macrophages, extracellular ATP now acts through its pyrophosphate chains, independently of other purine receptors, to inhibit IL-1beta release by other stimuli through two independent mechanisms: inhibition of ROS production and trapping of the inflammasome complex through intracellular clustering of actin filaments. |
